Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within ACT-GLOBAL Adaptive Platform Trial

The mRS is a 7-outcome ordered categorical scale that assesses functional neurological status after stroke. It is not intended for use as a measure of historical functional status. It is well accepted as a standard outcome around the world in the stroke community, by patients and by regulatory authorities. The seven values and the clinical summary of the individual scores are summarized in the following:

0 = No symptoms

• = No significant disability; able to carry out all usual activities
• = Slight disability; can look after own affairs, but unable to carry out all previous activities
• = Moderate disability; require some help
• = Moderately severe disability; unable to attend to own bodily needs without assistance
• = Severe disability; bedridden and requiring constant nursing care and attention
• = Dead

Excellent functional neurological outcome refers to mRS 0-1. The minimum mRS is 0 (no symptoms) while the maximum mRS is 6 (death). The higher the mRS score is the worse outcome is.

Independent functional neurological outcome refers to mRS 0-2. The minimum mRS is 0 (no symptoms) while the maximum mRS is 6 (death). The higher the mRS score is the worse outcome is.

Health Related Quality of Life is based on EuroQol 5 Dimension 5 Level (EQ-5D-5L). The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The version of the instrument selected for the trial is interviewer administered either in-person, or by telemedicine or by telephone.

Mortality refers to the state of being not alive.

The modified Rankin scale (mRs) is an ordinal disability score of 7 categories (0 = no symptoms to 6 = dead). The distribution of mRs scores across its different strata in patients will be calculated.

The NIHSS is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity. The scale includes measures of level of consciousness, extra ocular movements, motor and sensory tests, coordination, language, and speech evaluations. The NIHSS will be administered at Baseline prior to each domain randomisation (unless specified otherwise in specific domains) and Day 2. The NIHSS as part of standard of care treatment may be used if an assessment was not done by clinical trial personnel.

Any ICH is defined as ICH of any type on brain imaging ≤2 days of treatment, identified by adjudicators.

Symptomatic ICH on follow-up imaging (up to 2 days from randomization) will be a reportable serious adverse event that is adjudicated centrally according to the standard approach of reporting symptomatic ICHs used in the Heidelberg classification.

As defined by the WHO International Drug Monitoring Centre (1994), an SAE is any untoward medical occurrence that is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; be an important medical event that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes previously listed.